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HDAC2 And HS3ST5 Antisense RNA 2 (HDAC2-AS2)
- Target
- HDAC2-AS2
- Molecular classification
- Long noncoding RNA (lncRNA), Antisense RNA, Other (noncoding RNA family, regulatory RNA)
01
Overview
HDAC2 And HS3ST5 Antisense RNA 2 (HDAC2-AS2) is a long noncoding antisense RNA transcript that regulates gene expression by influencing HDAC2 mRNA transcription, primarily through transcriptional suppression and modulation of post-transcription end-site regulatory RNAs. It contributes to cancer progression, notably in HBV-associated hepatocellular carcinoma, by impairing cytotoxic CD8+ T cell function through interaction with cytosolic CDK9 and promoting immune cell exhaustion. HDAC2-AS2 is enriched in tumor-derived extracellular vesicles and is being explored as both a biomarker and a target for therapeutic intervention, particularly in cancer immunotherapy.
- Other names
- ENST00000421891HDAC2-AS2LOC107986638
02
Mechanism of action
ASOs: Bind and degrade HDAC2 mRNA and related regulatory RNAs, leading to reduced gene/protein expression and altered transcription Modulation of cytoplasmic CDK9 by HDAC2-AS2: HDAC2-AS2 binds CDK9, leading to decreased CDK9 protein in CD8+ T cells, promoting exhaustion and immunosuppression
03
Biological functions
Regulates expression of target genes, including HDAC2Modulates immune response by suppressing CD8+ T cell cytotoxicityPromotes exhaustion of PD-1+ CD8+ T cellsMay function in transcriptional regulation via antisense mechanisms and extra-coding RNA activity
04
Disease associations
Cancer (Hepatocellular carcinoma, HCC)Possibly neurological disorders (indirectly, due to HDAC2 involvement in memory and neurobiology)Other (potential roles in immune regulation and tumor microenvironment)
05
Safety considerations
Targeting HDAC2-AS2 or HDAC2 could affect immune function and memory, raising concerns of cognitive or immunological side effectsOff-target effects and specificity of ASOs remain a practical challenge
06
Interacting drugs
Antisense oligonucleotides (ASOs) targeting HDAC2 with downstream effects on HDAC2-AS2
1 more in the full profile.
07
Biomarkers
Elevated HDAC2-AS2 levels in circulating extracellular vesicles (EVs) from HCC patient plasma serve as a potential biomarker for prognosis and response to immunotherapy
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